The present invention relates to sample processing systems and methods. More particularly, the present invention provides devices, methods, and systems for processing sample materials.
Many different chemical, biochemical, and other reactions are sensitive to temperature variations. The reactions may be enhanced or inhibited based on the temperatures of the materials involved. Although it may be possible to process samples individually and obtain accurate sample-to-sample results, individual processing can be time-consuming and expensive.
Examples of some thermal processes that may be sensitive to temperature variations include, e.g., the manipulation of nucleic acid samples to assist in the deciphering of the genetic code. See, e.g., T. Maniatis et al. Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory (1982). Nucleic acid manipulation techniques include amplification methods such as polymerase chain reaction (PCR); target polynucleotide amplification methods such as self-sustained sequence replication (3SR) and strand-displacement amplification (SDA); methods based on amplification of a signal attached to the target polynucleotide, such as xe2x80x9cbranched chainxe2x80x9d DNA amplification; methods based on amplification of probe DNA, such as ligase chain reaction (LCR) and QB replicase amplification (QBR); transcription-based methods, such as ligation activated transcription (LAT) and nucleic acid sequence-based amplification (NASBA); and various other amplification methods, such as repair chain reaction (RCR) and cycling probe reaction (CPR). Other examples of nucleic acid manipulation techniques include, e.g., Sanger sequencing, ligand-binding assays, etc.
One approach to reducing the time and cost of thermally processing multiple samples using such techniques is to use a device including multiple chambers in which different portions of one sample or different samples can be processed simultaneously. Although widely accepted standardized systems have been developed using microtiter plates having, e.g., 96, 384 or more wells arranged in rectangular arrays to speed the processing of multiple sample, even faster sample processing is still desired.
One disadvantage of many devices designed to provide faster processing is, however, their non-standard format as compared to, e.g., the widely accepted standard microtiter plates including wells arranged in rectangular arrays. As a result, it may be prohibitive in terms of, e.g., equipment costs, test result acceptance, etc. for a facility to abandon the industry standard processes completely and adopt a new test methodology and new equipment.
The present invention provides devices, methods, and systems for processing sample materials that may be presented in a standard microtiter plate. More particularly, the present invention provides a bridge between standard microtiter plate systems, methods, protocols, etc. (that include wells arranged in rectangular arrays) and rotating sample processing devices and systems that allow users to obtain the rapid processing advantages of the more advanced sample processing devices.
The sample processing devices of the present invention preferably include a rectangular body to improve compatibility of the sample processing devices of the present invention with equipment designed for use with more conventional microtiter plates (which are typically rectangular in shape). Slight deviations from a true rectangle in the shape of the body are considered to fall within the scope of the present invention, although the body should have four identifiable corners at the junctions of four identifiable sides and two major surfaces. The sides need not necessarily form straight lines, although it may be preferred that the sample processing devices fit within the rectangular form factor of conventional microtiter plates.
The sample processing devices of the present invention include at least one set of process chambers arranged in one or more circular arcs such that the process chambers can be, e.g., located in contact with a circular thermal control ring. As a result, the sample processing device can be rotated during thermal cycling of the sample materials in the process chambers. Rotation of sample processing devices provides a number of advantages including, but not limited to assisting in the movement of sample materials between chambers in the sample processing devices and retention of sample materials in the desired chambers during processing (by virtue of the centrifugal forces acting on the sample materials during rotation).
Additional advantages of rotational processing including the facilitation of energy delivery to those chambers that are arranged in circular arcs by rotating the chambers such that they pass through a stationary beam of energy (e.g., laser energy, light, etc.). Those same advantages may also be available within the chambers arranged in circular arcs when employing detection methods in which the rotating chambers pass through a stationary detection system, e.g., a laser-based fluorescent detection.
Further, rotation of the sample processing devices may assist in thermal control of the sample materials by removing thermal energy using convection and conduction as air or other fluids move over the surface of the rotating sample processing devices.
The sample processing devices of the present invention also include input chambers and/or output chambers that are arranged on the sample processing devices in rectilinear grid arrays, thereby providing users with the ability to use equipment designed to process devices providing materials arranged in rectilinear grid arrays, e.g., microtiter plates, etc. For example, if the input chambers are arranged in a rectangular array, a conventional robotic pipetting tool may be used to deliver sample materials and/or reagents to the input chambers. Alternatively, or in addition to the rectangular arrangement of the input chambers, it may be possible to retrieve or monitor sample materials located in output chambers using conventional microtiter plate equipment if the output chambers are also arranged in rectangular arrays on the sample processing devices of the present invention.
In one aspect, the present invention provides a sample processing device including a rectangular body with a pair of opposing major surfaces and a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body.
In another aspect, the present invention provides a sample processing device including a rectangular body with a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body. The input chambers of the plurality of first process arrays and the input chambers of the plurality of second process arrays are arranged in rectilinear grid array; the output chambers of the first process arrays of the plurality of first process arrays are arranged in a rectilinear grid array; and the output chambers of the second process arrays of the plurality of second process arrays are arranged in a rectilinear grid array.
In another aspect, the present invention provides a sample processing device including a body with a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body, and further wherein the output chambers of the plurality of first process arrays are arranged in a rectilinear grid array; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body, and further wherein the output chambers of the plurality of second process arrays are arranged in a rectilinear grid array.
In another aspect, the present invention provides a sample processing device including a body with a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body, and further wherein the input chambers of the plurality of first process arrays are arranged in a rectilinear grid array; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body, and further wherein the input chambers of the plurality of second process arrays are arranged in a rectilinear grid array.
In another aspect, the present invention provides a sample processing device including a rectangular body and a plurality of first process arrays located within the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber. The primary process chambers of the plurality of process arrays are arranged in a circular arc and the input chambers of the plurality of first process arrays are arranged in rectilinear grid array.
In another aspect, the present invention provides a method of using a sample processing device, the method including providing a sample processing device that includes a rectangular body with a pair of opposing major surfaces and a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body. The method further includes loading sample material in the input chambers of at least some of the first and second process arrays; and transporting the sample material from the input chambers to at least some of the primary process chambers by rotating the sample processing device about an axis of rotation extending through the center of the body, wherein the primary process chambers are located further from the axis of rotation than the input chambers.
In another aspect, the present invention provides a method of using a sample processing device, the method including providing a sample processing device with a body including a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body, and further wherein the output chambers of the plurality of first process arrays are arranged in a rectilinear grid array; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body, and further wherein the output chambers of the plurality of second process arrays are arranged in a rectilinear grid array. The method further includes loading sample material in the input chambers of at least some of the first and second process arrays; and transporting the sample material from the input chambers to at least some of the primary process chambers by rotating the sample processing device about an axis of rotation extending through the center of the body, wherein the primary process chambers are located further from the axis of rotation than the input chambers.
In another aspect, the present invention provides a method of using a sample processing device, the method including providing a sample processing device including a body with a center, a first portion, and a second portion, wherein the first portion and the second portion are located on opposite sides of the center; a plurality of first process arrays located within the first portion of the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of process arrays are arranged in a circular arc about the center of the body, and further wherein the input chambers of the plurality of first process arrays are arranged in a rectilinear grid array; and a plurality of second process arrays located within the second portion of the body, each of the second process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber, wherein the primary process chambers of the plurality of second process arrays are arranged in a circular arc about the center of the body, and further wherein the input chambers of the plurality of second process arrays are arranged in a rectilinear grid array. The method further includes loading sample material in the input chambers of at least some of the first and second process arrays; and transporting the sample material from the input chambers to at least some of the primary process chambers by rotating the sample processing device about an axis of rotation extending through the center of the body, wherein the primary process chambers are located further from the axis of rotation than the input chambers.
In another aspect, the present invention provides a method of using a sample processing device by providing a sample processing device that includes a rectangular body and a plurality of first process arrays located within the body, each of the first process arrays including an input chamber, an output chamber, and a primary process chamber located between the input chamber and the output chamber. The primary process chambers of the plurality of process arrays are arranged in a circular arc and the input chambers of the plurality of first process arrays are arranged in rectilinear grid array. The method further includes loading sample material in the input chambers of at least some of the first process arrays, and transporting the sample material from the input chambers to at least some of the primary process chambers by rotating the sample processing device about an axis of rotation located outside of the body, wherein the primary process chambers are located further from the axis of rotation than the input chambers.
These and other features and advantages of the present invention are described with respect to illustrative embodiments of the invention presented below.